IJRPC 2014, 4(3), 723-734 Sabrein Harbi Mohamed et al. ISSN: 22312781 INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Research Article CHEMICALLY MODIFIED CARBON PASTE SENSORS FOR DETERMINATION OF CLOMIPRAMINE HYDROCHLORIDE IN PHARMACEUTICAL FORMULATIONS Yousry Moustafa Issa1, Sabrein Harbi Mohamed1* and Shaimaa Elfeky2 1Chemistry Department, Faculty of Science, Cairo University. 2Egyptian Chemistry Administration, Cairo, Egypt. ABSTRACT Chemically modified carbon paste sensors (CMCPSs) for determination of clomipramine hydrochloride (CLP.HCl) were prepared based on the use of ion-exchange compounds of clomipramine-tetraphenylborate(CLP-TPB) and clomipramine-silicotungestate(CLP-ST) as the electroactive materials.The potential response measurements showed that the best performance was exhibited by the sensors with composition 2% CLP-TPB, 49% o-NPPE and 49% graphite powder and 7% CLP-ST, 46.5% o-NPOE and 46.5 graphite powder.The sensors were found to be sensitive, precise and functional in the concentration ranges of 3.74×10-6-1.00×10-2 and 3.98×10-6-1.00×10- 2 -1 mol L at 25±1 ºC over the pH range 2.10-7.57 and 2.00-7.34 with slopes of 60.53±0.14 and -1 59.22±0.12 mV decade for CLP-TPB and CLP- ST sensors, respectively. The detection limitsand -6 -6 -1 limits of quantification were calculated to be 2.70×10 and 8.99×10 mol L for CLP-TPB and 2.26×10-6and 7.52×10-6mol L-1for CLP-ST sensors. The response time is about 10 s for both sensors.The selectivity studies showed that these sensors have higher selectivity towardCLP.HCl over a large number of cations and molecules. These sensors are successfully used for estimation of CLP.HCl in pharmaceutical formulation. The suggested method was validated by its comparison with the pharmacopeial one using t- and F-tests. The repeatability, reproducibility, ruggedness and robustness of the proposed methods were studied. Keywords: Clomipramine hydrochloride. Chemically modified carbon paste sensor. INTRODUCTION Clomipramine hydrochloride (CLP.HCl),3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N- dimethylpropan-1-amine hydrochloride, molar mass 351.3 g mol-1, scheme 1, is a tricyclic antidepressant1 belonging to dibenzazepine class of drugs. It is a psychiatric medication used to treat and relief symptoms of depressive and obsessive-compulsive disorders2 by inhibiting the reuptake of serotonin3 by blocking its transporters, serotonin isneureotransmitter present naturallyin the brain and it is needed to maintain mental balance. N N .HCl Scheme 1: Chemical structure of clomipramine hydrochloride 723 IJRPC 2014, 4(3), 723-734 Sabrein Harbi Mohamed et al. ISSN: 22312781 Several analytical methods have been reported for the determination of CLP.HCl in pharmaceutical formulations and biological fluids including spectrophotometric4,5,chemiluminescence 6,7,spectrofluorimetric8,9, capillary zone electrophoresis10,11, high-performance liquid chromatography12,13, gas chromatography14,15,liquid chromatography-mass spectrometry16, gas chromatography-mass spectrometry17. Most of these methods require the use of relatively costly sophisticated apparatus and complicated pre-treatment procedures like extraction of the active component. These requirements make it difficult for such methods to be used in routine analysis of large number of samples. As a result, suggesting of electrochemical methods of analysis using ion- selective sensors is an attractive alternative method for organic and inorganic detection, due to its advantages of being simple, rapid, reliable, low cost and non-destructive. Revealing the literature review, few potentiometric methods were found for determination of CLP.HCl18,19. Hence, the present work aims to develop twochemically modified carbon paste sensors for determination of CLP.HCl and to study their performance characteristics and their appliciability in potentiometric determination of CLP.HCl in pure solution, pharmaceutical formulations. These sensors are based on incorporation ofCLP-TPB and CLP-ST in spectroscopic graphite powder plasticized with o-nitrophenyl phenyl ether (o-NPPE) and o-nitrophenyloctyl ether (o-NPOE), respectively. MATERIALS AND METHODS Reagents and materials All reagents and chemicals used were of analytical grade purity and all solutions were prepared in bidistilled water. ClompramineHCl and its pharmaceutical formulations (Anafronil tablets, 25 and 50 mg/tablet) were obtained from NOVARTIS PHARMA S.A.E. Cairo, Egypt. Sodium tetraphenylborate (NaTPB) Na[C24H20B], silicotungestic acid (STA) (H4[W12SiO40]), dibutyl phthalate (DBP), dioctyl phthalate (DOP), tricresyl phosphate (TCP), ethylhexyladipate (EHA), o-nitrophenyl phenyl ether (ONPPE), ethylhexylsebacate (EHS), o-nitrophenyloctyl ether (ONPOE), dioctylsebacate (DOS) and graphite powder were obtained from Sigma-Aldrich, USA. 0.1 mol L-1solution of CLP.HCl was prepared by dissolving 3.513 g in 100 cm3bidistilled water. The working standard solutions (1.00×10-7-1.00×10-2mol L-1) were prepared by proper dilution of the stock solution with bidistilled water. A 1.00×10-2mol L-1NaTPB standard solution was prepared by dissolving 0.3422 g into 100 mL bi distilled water. Solutions of sodium hydroxide and hydrochloric acid of concentrations within the range 0.1-1.0 mol L-1were used for adjusting the pH of the medium. The stock solutions and the dilutions were kept in dark brown bottles in the refrigerator. To investigate the selectivity of the proposed electrodes, 0.1 mol L-1chloride solutions of Na+, K+, + 2+ 2+ 2+ 3+ NH4 , Ca , Cu , Mg , nitrate solution of Fe (obtained from Adwic chemical company, Abu Zabal, Egypt), sucrose, lactose, DL-histidine, L-cysteine, DL-asparagine, L-threonine, D-alanine and DL- serine (obtained from Aldrich chemical company) were prepared. Apparatus The potentiometric and pH measurements were carried out with a Jenway 3010 digital pH/mV meter. A techne circulator thermostat Model C-100 (Cambridge, England) was used to control the temperature of the test solution. A saturated calomel electrode (SCE) was used as the external reference. The electrochemical system of the CLP-CMCPS would be represented as CMCPS|testsolution|SCE. The elemental analysis of the prepared ion-exchangers was performed using automatic CHN analyzer (Perkin-Elmer model 2400) at the Micro-Analytical Center, Faculty of Science, Cairo University. Preparation of the ion-exchangers CLP-TPB and CLP-ST were prepared by mixing 50 mL of 1.00×10-2mol L-1CLP.HCl with 50 mL of 1.00×10-2mol L-1NaTPB or 0.25×10-2mol L-1STA. The resulting precipitates were left in contact with their mother liquor overnight to assure complete coagulation. The precipitates were then filtered, washed thoroughly with distilled water, dried at room temperature and then ground to fine powder to be used in the construction of the sensors. Preperation of the sensors The modified paste was prepared by mixing various amounts of CLP-TPB or CLP-ST (1-10%, w/w) and an appropriate amount of spectroscopic graphite powder (diameter, 1-2 µm) with plasticizer (ratio of graphite powder to plasticizer was 1:1, w/w). The mixture was carefully homogenized using agate pestle in agate mortar. After homogenization of the mixture, the paste was moved to a hole (7 mm diameter and 3.5 mm depth) at one end of a teflon holder (12 cm) and to the other end a stainless steel rod was inserted through the center of the holder to make electrical contact. This rod can move 724 IJRPC 2014, 4(3), 723-734 Sabrein Harbi Mohamed et al. ISSN: 22312781 up and down by screw movement to press the paste down when renewal of the electrode surface is needed. The external surface of the carbon paste was smoothed with soft paper. Construction of calibrations graphs Suitable increments of standard drug solution were added to 50 mLbidistilled water so as to cover the concentration range 1.00×10-7-1.00×10-2mol L-1. The working sensor and reference sensors were immersed in the solution and the emf values were recorded at 25±1.0 ºC, after each addition. The recorded values were plotted versus -log [CLP.HCl]. Effect of pH The effect of pH of the drug solution on the cell emf values in concentrations, 1.00×10-4, 5.00×10-4 and 1.00×10-3 mol L-1was studied. Aliquots of drug solution (50 mL) were transferred to the titration cell and the tested sensor in conjunction with a saturated calomel electrode was immersed in this solution. The emf and pH readings were simultaneously recorded. The pH of the solution was varied over range of 1.0-12.0 by addition of very small volumes of 1.0 mol L-1HCl or 0.1-1.0 mol L-1NaOH solutions. The emf readings were plotted against the pH for the different drug concentrations. Effect of temperature To study the temperature effect of the sensors, calibration graphs were constructed at different test solution temperatures (t) covering the range of 25-55 ºC with the aid of a circular thermostat Model C- 100 (Cambrige, England). The slope, the standard sensor potential (Eºsen), usable concentration ranges and response time of the sensor corresponding to each temperature were calculated in this temperature range. For the determination of the temperature coefficients of the sensors, the values of Eº were plotted versus (t-25). The slope of the straight line obtained represents the thermal coefficient (dEº/dt) which was calculated for each sensor using the following equation25: Eºcell=Eº25ºC + (dEº/dt) (t-25) Plot of Eºcell versus (t-25) produced a straight line whose slope is taken as the thermal coefficient of the cell. The values of the standard potentials of the sensors (Eºsen) were calculated after subtraction of the potential of the calomel electrode at different temperatures. Effect of interfering ions The selectivity coefficient values were calculated by applying the matched potential method26.